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Background: The factors related to emergency intervention for internal medicine conditions leading to airway obstruction are not clear., Objective: We aimed to identify factors associated with emergency interventions in acute airway obstructive diseases (AAODs)., Methods: This is a retrospective observational single-center study. We defined AAODs as acute epiglottitis, peritonsillar abscess, tonsillitis, pharyngitis, oral floor abscess, neck abscess, angioedema, Lemierre's syndrome, hemoptysis, and airway foreign body. We compared the group required airway interventions (intubation, cricothyroidotomy, tracheostomy) with the group treated conservatively admitted to Yokosuka Kyosai Hospital, Japan (tertiary referral hospital) for AAOD between April 2012 and March 2022., Results: Two hundred fifty-five patients were admitted for AAOD, 104 patients were excluded, and 150 patients (39 intervention group, 111 conservative group) were analyzed. Univariate analysis revealed significant age differences (74(61-78) vs 67(31-76), p<0.01), Glasgow Coma Scale (15(14-15) vs 15(15-15), p<0.01), respiratory rate (24(20-30) vs 20(16-22), p<0.01), National Early Warning Score (NEWS) (6(3-9) vs 3(1-5), p<0.01), Sequential Organ Failure Assessment (SOFA) score (2(1-4) vs 0(0-2), p<0.01), stridor (26% vs 2%, p<0.01), dysphagia (41% vs 21%, p=0.02), drooling (18% vs 3%, p<0.01), frequent suctions (6% vs 0%, p<0.01), airway examination abnormalities (AEAs) (69% vs 32%, p<0.01) and diagnosis (p<0.01). Multivariate logistic regression analysis indicated AEA (OR=9.41, 95%CI 3.66-24.2), upper airway diseases (OR=5.74, 95%CI 2.12-15.6), and SOFA score (OR=2.88, 95%CI 1.06-7.83) were predictors for intervention. However, the sensitivity and specificity of AEA were 0.69 (95%CI 0.52-0.83) and 0.69 (95%CI 0.59-0.77), respectively., Conclusions: AEAs were associated with a high risk of airway interventions in AAOD. Nevertheless, the sensitivity and specificity were insufficient., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Yokosuka Kyosai Hospital Institutional Review Board issued approval 22-55. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Suzuki et al.)

In this study, novel phosphorescent dipyrido[3,2- a ;2'3'- c ]phenazine (dppz)-platinum(II)-phenylacetylide complexes were developed to fabricate non-doped organic light-emitting diodes (OLED) by solution-processing. To facilitate the charge carrier injection into the emitting layer (EML), 3,6-di- tert -butylcarbazole-functinalized phenylacetylides were employed. As for the dppz ligand, 9,9-dihexylfluoren-2-yl and 4-hexylthiophen-2-yl side-arms were introduced to the 2,7-positions, which led to reddish orange and red photoluminescence (PL), respectively, in solution and film states (PL wavelength: ca. 600 and ca. 625 nm, respectively). The carbazole-appended phenylacetylide ligands hardly affected the emission color, although unsubstituted phenylacetylides gave rise to aggregate- or excimer-based near-infrared PL with a low quantum yield. Two types of non-doped OLEDs were fabricated: single-layer and multilayer devices. In both devices, the organic layers were fabricated by spin-coating, and the EML consisted of a neat film of the corresponding platinum(II) complex. Therein, electroluminescence spectra corresponding to those of PL were observed. The single-layer devices exhibited low device efficiencies due to a deteriorated charge carrier balance. The multilayer devices possessed hole- and electron-transporting layers on the anode and cathode sides of the EML, respectively. Owing to an improved charge carrier balance, the multilayer devices exhibited higher device performance, affording considerably improved values of luminance and external quantum efficiency.

Numerous fluorescent dye-based optical sensors have been developed to detect water in organic solvents. However, only a few such sensors can detect water in polar solvents such as methanol or dimethyl sulfoxide, and their detection range is generally narrow. Therefore, in this study, a copolymer membrane incorporated with a pyridinium betaine dye (denoted PB1), which exhibited intramolecular charge transfer (ICT) characteristics, was developed to realise simple water detection in organic solvents. The pyridinium betaine structure, comprising intramolecular hydrogen bonds between the oxygen in the maleimide moiety and the hydrogen in the pyridinium, was vital for achieving efficient fluorescence emission. The membrane was prepared by copolymerising PB1 with the N , N -dimethyl acrylamide/acrylamide monomer on a glass plate, and the fluorescence in water-mixed organic solvents was investigated ( λ abs = 490 nm, λ fl = 630 nm). The fluorescence intensity of the dye-immobilised membrane decreased with increasing water content of the organic solvents. The detection ranges in tetrahydrofuran, ethanol, methanol, and dimethyl sulfoxide were approximately <40, <40, <40, and <60 vol% water, respectively. In contrast, membranes based on a quaternary pyridinium dye (without intramolecular hydrogen bonds) did not detect water in methanol and dimethyl sulfoxide, although it was more sensitive than PB1 in the narrow region of low water concentration in THF. Theoretical calculations corroborated the importance of the pyridinium betaine structure in detecting water in organic solvents, with the increase in polarity and the formation of intermolecular hydrogen bonds between PB1 and water found to induce molecular rotation and fluorescence quenching.

Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood-onset psychiatric disorder. We investigated the effects of systemic administration of monoamine reuptake inhibitors on long-term potentiation (LTP) formation and monoamine release in the medial prefrontal cortex (mPFC) of the stroke-prone spontaneously hypertensive rat (SHRSP)/Ezo, an animal model of ADHD, and its genetic control, Wistar Kyoto (WKY)/Ezo, to elucidate the functional changes in the mPFC monoamine neural system. Methylphenidate (dopamine (DA) and noradrenaline (NA) reuptake inhibitor) and desipramine (NA reuptake inhibitor) improved LTP formation defects in the mPFC of SHRSP/Ezo, suggesting that NA or both DA and NA are required for improvement of impaired LTP. Methylphenidate increased mPFC DA in both WKY/Ezo and SHRSP/Ezo, but the increase was greater in the former. GBR-12909 (DA reuptake inhibitor) increased mPFC DA in WKY/Ezo but had no effect in SHRSP/Ezo. This may be because DA transporter in SHRSP/Ezo is functionally impaired and contributes less to DA reuptake, so its inhibition did not increase DA level. Meanwhile, basal DA levels in the mPFC of SHRSP/Ezo were paradoxically decreased. These results suggest that functional changes in the DA and NA neural system in the frontal lobe are involved in the pathology of ADHD., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2023 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Aim This study aimed to investigate the appropriate endotracheal tube (ETT) position during percutaneous dilatational tracheostomy (PDT). Methods This single-center observational study included hospitalized patients who underwent surgical tracheostomy (ST) between August 2021 and October 2022. During ST, the trachea was opened, and the ETT was pulled out visually. It stopped when the ETT was no longer visible, and the tracheostomy tube was placed in the trachea. The ETT position was measured by considering the ETT position during ST to be the appropriate position during PDT. The correlation between the measured ETT position and patient characteristics was evaluated. A prediction equation for the ETT position was derived from the derivation group, and validation of the prediction equation was evaluated by the validation group. Results Forty-six and 15 patients were in the derivation and validation groups, respectively. Weight, duration of intubation, and in-hospital mortality were significantly different between the two groups. The measured ETT position correlated with body height (r=0.60, p<0.001) and sex (r=0.45, p=0.002), while the ETT position before ST showed a weak correlation (r=0.34, p=0.020). The predicted and measured values in the validation group correlated with each other (r=0.58, p=0.024). Conclusion The appropriate ETT position for PDT correlates with body height, and the equation "body height×0.112-0.323 cm" was derived. This predictive equation may be useful as a guide for ETT positioning during PDT puncture., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Michishita et al.)

The photophysical properties of dyes composed of two squaraine chromophores fused with a benzodipyrrole central moiety (BS1 and BS2), were investigated using steady-state absorption, fluorescence, and transient absorption spectroscopy. The dyes exhibit solvent-independent split electronic absorption due to exciton-coupling. Interestingly significant solvent-dependent fluorescence properties were observed. In toluene, they emit from the lowest excited state, while in methanol, they show weak emission in the higher energy region. In the low-temperature glass matrix, emission from the lowest excited state dominates similarly to that in toluene. The transient absorption spectra exhibit similar ground-state bleaching in toluene and methanol, revealing the formation of delocalized excited states by exciton coupling independent of solvent. However, the excited state deactivates rapidly in ultrafast time scale in methanol, likely due to solvent interaction, leading to rapid non-radiative deactivation. The PEG film doped with the exciton-coupled bis-squaraine shows a distinct fluorescence response to methanol vapor., (© 2023 Wiley-VCH GmbH.)

Background: Although Chlamydophila pneumoniae (CP)is known to play a role in atherosclerosis and endothelial injury, its past infection on the mortality of coronavirus disease 2019 (COVID-19), which was also reported to be a vascular disease, remains unknown., Methods: In this retrospective cohort study, we examined 78 COVID-19 patients and 32 bacterial pneumonia patients who visited a tertiary emergency center in Japan between April 1, 2021, and April 30, 2022. CP antibody levels, including IgM, IgG, and IgA, were measured., Results: Among all patients, the CP IgA-positive rate was significantly associated with age (P = 0.002). Between the COVID-19 and non-COVID-19 groups, no difference in the positive rate for both CP IgG and IgA was observed (P = 1.00 and 0.51, respectively). The mean age and proportion of males were significantly higher in the IgA-positive group than in the IgA-negative group (60.7 vs. 75.5, P = 0.001; 61.5% vs. 85.0%, P = 0.019, respectively). Smoking and dead outcomes were significantly higher both in the IgA-positive group and IgG-positive group (smoking: 26.7% vs. 62.2, P = 0.003; 34.7% vs. 73.1%, P = 0.002, dead outcome: 6.5% vs. 29.8%, P = 0.020; 13.5% vs. 34.6%, P = 0.039, respectively). Although the log-rank test revealed higher 30-day mortality in the IgG-positive group compared to the IgG-negative group (P = 0.032), Cox regression analysis demonstrated no significant difference between the IgG-positive and negative groups (hazard ratio (HR) = 4.10, 95%CI = 0.94-18.0, P = 0.061)., Conclusion: The effect of past CP infection on 30-day mortality in COVID-19 patients was not obvious., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Horiuchi et al.)

Oxocarbon derivatives consisting of 4- and 5-membered rings, referred to as croconaine and squaraine dyes and regarded as closed-shell molecules, are found to have an intermediate open-shell character from the experimental results of 1 H-NMR, ESR spectroscopy, SQUID magnetometric analysis, and X-ray crystallography. We employed two chalcogenopyrylium moieties with O and S chalcogen atoms as substitutions on oxocarbons. The singlet-triplet energy gaps (Δ E S-T ) associated with the degree of diradical nature are smaller for croconaines than for squaraines and smaller for thiopyrylium than for pyrylium groups. The diradical nature impacts the electronic transition energy that decreased with a decreasing degree of diradical contribution. They exhibit substantial two-photon absorption in the region over 1000 nm. The diradical character y of the dye was determined experimentally from the observed one- and two-photon absorption peaks and the triplet energy level. The present finding provides new insight into diradicaloids with the contribution of non-Kekulé oxocarbon and also showcases the correlation between the electronic transition energy and their diradical character., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Aim: Coronavirus disease 2019 pneumonia differs from ordinary pneumonia in that it is associated with lesions that reduce pulmonary perfusion. Dual-energy computed tomography is well suited to elucidate the etiology of coronavirus disease 2019 pneumonia, because it highlights changes in organ blood flow. In this study, we investigated whether dual-energy computed tomography could be used to determine the severity of coronavirus disease 2019 pneumonia., Methods: Patients who were diagnosed with coronavirus disease 2019 pneumonia, admitted to our hospital, and underwent dual-energy computed tomography were included in this study. Dual-energy computed tomography findings, plane computed tomography findings, disease severity, laboratory data, and clinical features were compared between two groups: a critical group (18 patients) and a non-critical group (30 patients)., Results: The dual-energy computed tomography results indicated that the percentage of flow loss was significantly higher in the critical group compared with the non-critical group ( P  < 0.001). Additionally, our data demonstrated that thrombotic risk was associated with differences in clinical characteristics ( P  = 0.018). Receiver operating characteristic analysis revealed that the percentage of flow loss, evaluated using dual-energy computed tomography, could predict severity in the critical group with 100% sensitivity and 77% specificity. However, there were no significant differences in the receiver operating characteristic values for dual-energy computed tomography and plane computed tomography., Conclusion: Dual-energy computed tomography can be used to associate the severity of coronavirus disease 2019 pneumonia with high accuracy. Further studies are needed to draw definitive conclusions., (© 2022 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Aim: This study compared the clinical outcomes of critically ill patients with coronavirus disease (COVID-19) pneumonia treated with high-dose methylprednisolone and other steroids., Methods: This retrospective observational study included critically ill COVID-19 pneumonia adult patients with tracheal intubation treated between April 1, 2020, and September 15, 2021. Of the 46 patients who met the inclusion criteria, 36 received steroid pulse therapy (Group P) and 10 received steroids without pulse therapy (Group NP). Subgroup analyses in Group P by methylprednisolone dose of 1000 or 500 mg for 3 days during intensive care unit stay were carried out. The primary and secondary outcomes were 28-day mortality and steroid-associated complications, respectively., Results: In the Kaplan-Meier curve analysis, there was no difference in the 28-day survival between P and NP groups (log-rank P  = 0.046). Univariate Cox proportional hazard model also showed that Group P had a decreased 28-day mortality (hazard ratio 0.30; [95% confidence interval, 0.20-0.44]; P  < 0.01). After adjusting for covariates (age, sex, remdesivir, baricitinib, and favipiravir), using the multivariate Cox proportional hazards model, Group P had improved 28-day mortality (0.50 [0.30-0.85], P  = 0.01)., Conclusion: Steroid pulse therapy might improve the 28-day and in-hospital mortality in critically ill patients with COVID-19 pneumonia., (© 2022 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

We developed a series of blue-emitting 1,8-naphthalimide dyes covalently attached to 2-(2-hydroxyphenyl)-2 H -benzotriazoles that retard photodegradation of the fluorophore. The dyes displayed weaker fluorescence emissions than the parent 1.8-naphthalimide. Quantum chemical calculations suggested that the decreased fluorescence was caused by the nonradiative deactivation promoted through the excited state intramolecular proton transfer (ESIPT) in benzotriazole components. The dyes' phosphorescences in a degassed solution at 77 K were more efficient than that of the parent 1.8-naphthalimide, indicating a possible deactivation pathway through intersystem crossing. PMMA films doped with these dyes showed higher resistance against photoaging than the film doped with an equimolar mixture of constituent 1.8-naphthalimide and the benzotriazole derivatives. Thus, the covalently linked benzotriazole units slow fluorophore degradation not only by preferential absorption of harmful UV light, which is found in the film with a simple mixture of two components, but also by the nonradiative deactivation involved in benzotriazole units., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Designing fluorescent molecules requires considering multiple interrelated molecular properties, as opposed to properties that straightforwardly correlated with molecular structure, such as light absorption of molecules. In this study, we have used a de novo molecule generator (DNMG) coupled with quantum chemical computation (QC) to develop fluorescent molecules, which are garnering significant attention in various disciplines. Using massive parallel computation (1024 cores, 5 days), the DNMG has produced 3643 candidate molecules. We have selected an unreported molecule and seven reported molecules and synthesized them. Photoluminescence spectrum measurements demonstrated that the DNMG can successfully design fluorescent molecules with 75% accuracy ( n = 6/8) and create an unreported molecule that emits fluorescence detectable by the naked eye.

[Purpose] This study aimed to identify the factors associated with exercise behavior in patients with peripheral arterial disease. [Participants and Methods] The study included 43 patients with peripheral arterial disease (mean age, 75.2 ± 5.6 years) who were admitted for endovascular treatment from January 2020 to June 2021. Participants were surveyed through questionnaires to assess their physical function for determining their exercise behavior and the presence of physical, personal, and environmental factors that might have affected their stage of change regarding exercise behavior. [Results] A comparison of physical, personal, and environmental factors between the two groups classified by the presence or absence of exercise behavior showed that subjective health and exercise self-efficacy were significantly lower in the group without exercise. Furthermore, a difference was noted in the presence or absence of work. The adjusted binomial logistic regression analysis results using each of the factors differing between the groups, plus the walking impairment questionnaire total score as explanatory variables, showed a significant relationship with exercise self-efficacy only. [Conclusion] The results of this study showed that exercise self-efficacy presented a useful predictive relationship with the presence of exercise behavior in patients with peripheral arterial disease., (2022©by the Society of Physical Therapy Science. Published by IPEC Inc.)

We report a new design strategy for an excited-state intramolecular proton transfer (ESIPT) fluorophore that can be used in acidic media. A photobasic pyridine-centered donor-acceptor-donor-type fluorophore is combined with a basic trialkylamine "strap". In the presence of an acid, protonation occurs predominantly at the amine moiety in the ground state. A single-crystal X-ray diffraction analysis confirmed the formation of a pre-organized intramolecular hydrogen-bonded structure between the resulting ammonium moiety and the pyridine ring. Upon excitation, the intramolecular charge-transfer transition increases the basicity of the pyridine moiety in the excited state, resulting in proton transfer from the amine to the pyridine moiety. Consequently, the fluorophore takes on a polymethine-dye character in the ESIPT state, which gives rise to significantly red-shifted emission with an increased fluorescence quantum yield., (© 2021 Wiley-VCH GmbH.)

Evaluation of the legume proportion in grass-legume mixed swards is necessary for breeding and for cultivation research of forage. For objective and time-efficient estimation of legume proportion, convolutional neural network (CNN) models were trained by fine-tuning the GoogLeNet to estimate the coverage of timothy (TY), white clover (WC), and background (Bg) on the unmanned aerial vehicle-based images. The accuracies of the CNN models trained on different datasets were compared using the mean bias error and the mean average error. The models predicted the coverage with small errors when the plots in the training datasets were similar to the target plots in terms of coverage rate. The models that are trained on datasets of multiple plots had smaller errors than those trained on datasets of a single plot. The CNN models estimated the WC coverage more precisely than they did to the TY and the Bg coverages. The correlation coefficients ( r ) of the measured coverage for aerial images vs. estimated coverage were 0.92-0.96, whereas those of the scored coverage by a breeder vs. estimated coverage were 0.76-0.93. These results indicate that CNN models are helpful in effectively estimating the legume coverage., Competing Interests: HN, MF, and NS were employed by company BANDAI NAMCO Research Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fujiwara, Nashida, Fukushima, Suzuki, Sato, Sanada and Akiyama.)

By combining video laryngoscopy and fiberoptic bronchoscopy, awake intubation can be performed more safely., Competing Interests: Nothing to declare., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Objective: This study aimed to clarify the effects of pre- and postoperative physical function on the 6-minute walking distance (6MWD) in patients with peripheral arterial disease (PAD)., Method: Forty-two elderly patients with PAD who were hospitalized for revascularization and able to walk independently were included in the study. The 6MWD, ankle brachial index (ABI), weight-bearing index (WBI), gait, and intermittent claudication distance (ICD) were measured before and after the surgery, and skeletal muscle index was measured only before surgery. Analyses were performed by comparing the pre- and postoperative values of each factor using a paired t-test. In addition, multiple regression analysis was performed with 6MWD as the dependent variable before and after surgery., Results: Postoperatively, pain disappeared in 22 patients, and ABI, ICD, 6MWD, and stride length improved significantly. ICD and stride length were extracted as factors related to 6MWD before and after surgery, and ABI, WBI, and stride length were extracted as factors related to 6MWD after surgery., Conclusion: The improvement of intermittent claudication associated with revascularization suggests a stronger influence of functional aspects on postoperative 6MWD., Competing Interests: The authors have no conflicts of interest to disclose., (2021, JAPANESE PHYSICAL THERAPY ASSOCIATION.)

Background: The coronavirus disease 2019 (COVID-19) pandemic rapidly increases the use of mechanical ventilation (MV). Such cases further require extracorporeal membrane oxygenation (ECMO) and have a high mortality., Objective: We aimed to identify prognostic biomarkers pathophysiologically reflecting future deterioration of COVID-19., Methods: Clinical, laboratory, and outcome data were collected from 102 patients with moderate to severe COVID-19. Interleukin (IL)-6 level and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA copy number in plasma were assessed with ELISA kit and quantitative PCR., Results: Twelve patients died or required ECMO owing to acute respiratory distress syndrome despite the use of MV. Among various variables, a ratio of oxygen saturation to fraction of inspired oxygen (SpO2/FiO2), IL-6, and SARS-CoV-2 RNA on admission before intubation were strongly predictive of fatal outcomes after the MV use. Moreover, among these variables, combining SpO2/FiO2, IL-6, and SARS-CoV-2 RNA showed the highest accuracy (area under the curve: 0.934). In patients with low SpO2/FiO2 (< 261), fatal event-rate after the MV use at the 30-day was significantly higher in patients with high IL-6 (> 49 pg/mL) and SARS-CoV-2 RNAaemia (> 1.5 copies/μL) compared to those with high IL-6 or RNAaemia or without high IL-6 and RNAaemia (88% vs. 22% or 8%, log-rank test P = 0.0097 or P < 0.0001, respectively)., Conclusions: Combining SpO2/FiO2 with high IL-6 and SARS-CoV-2 RNAaemia which reflect hyperinflammation and viral overload allows accurately and before intubation identifying COVID-19 patients at high risk for ECMO use or in-hospital death despite the use of MV., Competing Interests: The authors have declared that no competing interests exist.

Background: This investigator-initiated, open-label, single-arm, single-institute study was conducted to investigate the effectiveness of induction combination chemoradiotherapy and long-term maintenance therapy with temozolomide (TMZ) plus interferon (IFN)-β for glioblastoma., Methods: The initial induction combination chemoradiotherapy comprised radiotherapy plus TMZ plus vincristine plus IFN-β. Maintenance chemotherapy comprised monthly TMZ, continued for 24-50 cycles, plus weekly IFN-β continued for as long as possible. The primary endpoint was 2-year overall survival (2y-OS). The study protocol was to be considered valid if the expected 2y-OS was over 38% and the lower limit of the 95% confidence interval (CI) was no less than 31.7% compared with historical controls, using Kaplan-Meier methods. Secondary endpoints were median progression-free survival (mPFS), median OS (mOS), 5-year OS rate (5y-OS), and mPFS and mOS classified according to MGMT promoter methylation status., Results: Forty-seven patients were analyzed. The 2y-OS was 40.7% (95%CI, 27.5-55.4%). The mPFS and mOS were 11.0 months and 18.0 months, respectively, and 5y-OS was 20.3% (95%CI, 10.9-34.6%). The mPFS in groups with and without MGMT promoter methylation in the tumor was 10.0 months and 11.0 months (p = 0.59), respectively, and mOS was 24.0 months and 18.0 months (p = 0.88), respectively. The frequency of grade 3/4 neutropenia was 19.1%., Conclusions: The 2y-OS with induction multidrug combination chemoradiotherapy and long-term maintenance therapy comprising TMZ plus IFN-β tended to exceed that of historical controls, but the lower limit of the 95%CI was below 31.7%. Although the number of cases was small, this protocol may rule out MGMT promoter methylation status as a prognostic factor., Trial Registration: University Hospital Medical Information Network (number UMIN000040599 )., (© 2021. The Author(s).)

Background/objectives: Severe acute pancreatitis (SAP) has a high mortality rate despite ongoing attempts to improve prognosis through a various therapeutic modalities. This study aimed to delineate etiology-based routes that may guide clinical decisions for the treatment of SAP., Methods: Using data from a recent retrospective multicenter study in Japan, we analyzed the association between clinical outcomes, mainly in-hospital mortality and pancreatic infection, and various etiologies while considering confounding factors. We performed additional multivariate analyses and built decision tree models., Results: The 1097 participating patients were classified into the following groups by etiology: alcohol (n = 436, 39.7%); cholelithiasis (n = 230, 21.0%); idiopathic (n = 227, 20.7%); and others (n = 204, 18.6%). Mortality at hospital discharge was 8.4%, 12.2%, 16.7%, and 16.2% in the alcohol, cholelithiasis, idiopathic, and others groups, respectively. According to multivariable analysis, early enteral nutrition (EN) was significantly associated with reduced in-hospital mortality only in the cholelithiasis group. However, there was a consistent association between age and the need for mechanical ventilation and increased mortality, regardless of etiology. Our decision tree models presented different contributing factors depending on the etiology and patient background. Interaction analysis showed that EN and the use of prophylactic antibiotics may influence these results differently according to etiology., Conclusions: No study has yet used comprehensive models to investigate etiology-related prognostic factors for SAP; our results can, therefore, be used as a reference for improving clinical decisions., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Ca 2+ -induced Ca 2+ release (CICR) via type-3 ryanodine receptor enhances neurotransmitter release in frog motor nerve terminals. To test a possible role of synaptic vesicle in CICR, we examined the effects of loading of EGTA, a Ca 2+ chelator, into synaptic vesicles and depolymerization of actin fibers. Intravesicular EGTA loading via endocytosis inhibited the ryanodine sensitive enhancement of transmitter release induced by tetanic stimulation and the associated rises in intracellular-free Ca 2+ ([Ca 2+ ] i : Ca 2+ transients). Latrunculin A, a depolymerizer of actin fibers, enhanced both spontaneous and stimulation-induced transmitter release, but inhibited the enhancement of transmitter release elicited by successive tetanic stimulation. The results suggest a possibility that the activation of CICR from mobilized synaptic vesicles caused the enhancement of neurotransmitter release., (© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Seckel syndrome (SS) is a rare spectrum of congenital severe microcephaly and dwarfism. One SS-causative gene is Ataxia Telangiectasia and Rad3-Related Protein (ATR), and ATR (c.2101 A>G) mutation causes skipping of exon 9, resulting in a hypomorphic ATR defect. This mutation is considered the cause of an impaired response to DNA replication stress, the main function of ATR, contributing to the pathogenesis of microcephaly. However, the precise behavior and impact of this splicing defect in human neural progenitor cells (NPCs) is unclear. To address this, we established induced pluripotent stem cells (iPSCs) from fibroblasts carrying the ATR mutation and an isogenic ATR-corrected counterpart iPSC clone. SS-patient-derived iPSCs (SS-iPSCs) exhibited cell type-specific splicing; exon 9 was dominantly skipped in fibroblasts and iPSC-derived NPCs, but it was included in undifferentiated iPSCs and definitive endodermal cells. SS-iPSC-derived NPCs (SS-NPCs) showed distinct expression profiles from ATR non-mutated NPCs with negative enrichment of neuronal genesis-related gene sets. In SS-NPCs, abnormal mitotic spindles occurred more frequently than in gene-corrected counterparts, and the alignment of NPCs in the surface of the neurospheres was perturbed. Finally, we tested several splicing-modifying compounds and found that TG003, a CLK1 inhibitor, could pharmacologically rescue the exon 9 skipping in SS-NPCs. Treatment with TG003 restored the ATR kinase activity in SS-NPCs and decreased the frequency of abnormal mitotic events. In conclusion, our iPSC model revealed a novel effect of the ATR mutation in mitotic processes of NPCs and NPC-specific missplicing, accompanied by the recovery of neuronal defects using a splicing rectifier.

Fluorophores that can undergo excited-state intramolecular proton transfer (ESIPT) represent promising scaffolds for the design of compounds that show red-shifted fluorescence. Herein, we disclose new near infrared-emissive materials based on a dialkylamine-strapped 2,5-dithienylpyrrole as an ESIPT scaffold. The introduction of electron-accepting units to the terminal positions of this scaffold generates acceptor-π-donor-π-acceptor (A-π-D-π-A) type π-conjugated compounds. Following the ESIPT, the electron-donating ability of the core scaffold increases, which results in a substantially red-shifted emission in the NIR region, while increasing the oscillator strength. The electron-accepting units play a vital role to achieve intense and red-shifted emission from the ESIPT state. The strapped dialkylamine chain that forms an intramolecular hydrogen bond is also essential to induce the ESIPT. Moreover, an extended A-π-D-π-A skeleton enables two-photon excitation with the NIR light. One of the derivatives that satisfy these features, i.e. , borylethenyl-substituted 5 , exhibited an intense NIR emission in polar solvents such as acetone ( λ em = 708 nm, Φ F = 0.55) with a strong two-photon-absorption band in the NIR region.

Obtaining highly purified differentiated cells via directed differentiation from human pluripotent stem cells (hPSCs) is an essential step for their clinical application. Among the various conditions that should be optimized, the precise role and contribution of the extracellular matrix (ECM) during differentiation are relatively unclear. Here, using a short fragment of laminin 411 (LM411-E8), an ECM predominantly expressed in the vascular endothelial basement membrane, we demonstrate that the directed switching of defined ECMs robustly yields highly-purified (>95%) endothelial progenitor cells (PSC-EPCs) without cell sorting from hPSCs in an integrin-laminin axis-dependent manner. Single-cell RNA-seq analysis revealed that LM411-E8 resolved intercellular transcriptional heterogeneity and escorted the progenitor cells to the appropriate differentiation pathway. The PSC-EPCs gave rise to functional endothelial cells both in vivo and in vitro. We therefore propose that sequential switching of defined matrices is an important concept for guiding cells towards desired fate.

We report the first examples of straightforward trans-hydroboration of internal alkynes at room temperature with 9-BBN, producing five-membered BN-heterocycles. Contrary to conventional cis-hydroboration, we demonstrate that the introduction of a pyridyl group switches the stereoselectivity of the reaction. A hydride migration mechanism has been proposed and supported by DFT calculations for the trans-hydroboration. This new hydroboration approach allows facile construction of new blue fluorescent BN-heterocyclic compounds.

Ladder π-conjugated materials and also push-pull systems belong to important classes of compounds for the development of organic electronic devices. In this communication, a novel π-conjugated material that unifies the properties of both of these classes is presented. The material comprises a rigid biphenyl framework, which bears two bridging electron-accepting phosphine oxide moieties as well as two electron-donating amino groups. The structure and photophysical properties of this compound are discussed and compared with those of a related system lacking the second P-moiety.

Fanconi anemia (FA) is a disorder of genomic instability characterized by progressive bone marrow failure (BMF), developmental abnormalities, and an increased susceptibility to cancer. Although various consequences in hematopoietic stem/progenitor cells have been attributed to FA-BMF, the quest to identify the initial pathological event is still ongoing. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts of six patients with FA and FANCA mutations. An improved reprogramming method yielded iPSC-like colonies from all patients, and iPSC clones were propagated from two patients. Quantitative evaluation of the differentiation ability demonstrated that the differentiation propensity toward the hematopoietic and endothelial lineages is already defective in early hemoangiogenic progenitors. The expression levels of critical transcription factors were significantly downregulated in these progenitors. These data indicate that the hematopoietic consequences in FA patients originate from the early hematopoietic stage and highlight the potential usefulness of iPSC technology for elucidating the pathogenesis of FA-BMF., (©AlphaMed Press.)

An amine-embedded flexible alkyl strap has been incorporated into an emissive boryl-substituted dithienylpyrrole skeleton as a new entity of excited-state intramolecular proton transfer (ESIPT) chromophores. The π-electron system shows a dual emission, which covers a wide range of the visible region depending on the solvent polarity. The incorporation of the aminoalkyl strap as well as the terminal boryl groups efficiently stabilize the zwitterionic excited-state species resulting from the ESIPT even in an aqueous medium., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Contamination of the external surface of anticancer drug vials supplied to hospital pharmacies has been recognized as a potential health hazard. The aim of this study was to investigate the levels of contamination on the exterior surface of vials containing platinum anticancer drugs in Japan. Platinum contamination on the exterior surface of vials containing cisplatin or carboplatin was examined using products commercially available in Japan. Cisplatin vials from 42 batches (2 drug contents, 10 products and 5 manufacturers) and carboplatin vials from 28 batches (3 drug contents, 7 products and 3 manufacturers) were used. Five vials were randomly sampled from each batch. Exterior contamination levels of 0.070-144 ng/vial as cisplatin and 0.21-1630 ng/vial as carboplatin were detected. Significant differences in the levels of contamination among the batch numbers were observed in 6 of 10 cisplatin products and 6 of 7 carboplatin products. Significant differences in the levels of contamination were observed in 3 cisplatin products with different contents of drug within the vials and 1 carboplatin product with different contents of drug within the vials. Significant differences in the contamination levels among the cisplatin manufacturers but not carboplatin manufacturers were observed. The degree of contamination of the carboplatin products was significantly higher than that of the cisplatin products. In conclusion, external contamination was confirmed in all cisplatin and carboplatin vials tested. The degree of contamination was different among different batch numbers, drug contents, manufacturers, and platinum anticancer drug.

Contamination of the exterior surface of vials of cytostatic drugs by the drugs themselves is a potential hazard to human health. This study developed a validated method using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the determination of contamination of the exteriors of vials of cisplatin and carboplatin. Large Alpha® sampling swabs were employed to wipe the vial exterior. Cisplatin or carboplatin and gold(III) as an internal standard were derivatized by N,N-diethyldithiocarbamate (DDTC). Pt(DDTC)(3)(+) and Au(DDTC)(2)(+) were monitored by the respective transitions of m/z 639.3-490.9 and 493.0-345.0, respectively. Each separation was completed within 9 min using a 3 μm particle ODS-column. Calibration curves for cisplatin and carboplatin were linear over concentration ranges of 30-10,000 and 30-30,000pgvial(-1), respectively. The accuracies and precisions were 96.1-102.5% and within 8.2% for intra-assay and 99.6-103.3% and within 7.6% for inter-assay, respectively. Their lower limit of quantification was 30 pg vial(-1). Amounts of 0.17-17.0 ng vial(-1) as cisplatin and 0.48-794 ng vial(-1) as carboplatin were detected from the exterior surface of the vials. This validated method using LC-ESI-MS/MS for the determination of platinum anticancer drugs is helpful for monitoring contamination of the exterior surface of drug vials., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Vortex shedding from an obstacle potential moving in a Bose-Einstein condensate is investigated. Long-lived alternately aligned vortex pairs are found to form in the wake, which is similar to the Bénard-von Kármán vortex street in classical viscous fluids. Various patterns of vortex shedding are systematically studied and the drag force on the obstacle is calculated. It is shown that the phenomenon can be observed in a trapped system.

An academic subcommittee of Japanese Society of Hospital Pharmacists formulated the guideline for the sterile preparation of antineoplastic agents in 2008. The practical methods to monitor a workplace contamination and occupational exposure to antineoplastic agents have not been introduced into a hospital setting yet. The aims of this study were to develop a monitoring method using doxorubicin for workplace contamination and occupational exposure to antineoplastic agents and to apply it to surveillance in a hospital setting. The surface contamination of workplace was wiped with non-woven fabric containing 70% 2-propanol. The occupational exposure was evaluated by spot urine sampling during 24 hours. Chromatographic separation was achieved by a reverse phase HPLC. Doxorubicin and fluorescein (internal standard) were detected at an excitation and emission wavelength of 470 and 550 nm, respectively. The monitoring method was applied to survey the workplace contamination and occupational exposure to antineoplastic agents in Hamamatsu University Hospital. The calibration curves for doxorubicin were linear over concentration ranges of 1.5-729 ng/100 cm(2) for surface contamination and 1.0-486 ng/ml for the urine. The run time was 10 min. The intra- and interassay precisions were within 8.5%. As the surveillance in a hospital setting, the flow line adhering to the guideline kept the exposure to low level. In addition, the occupational exposure in the workers was not observed. In conclusion, this study developed the monitoring method using doxorubicin for the workplace contamination and occupational exposure to antineoplastic agents. This method can be utilized to survey in a hospital setting.

Superficial siderosis of the central nervous system (SS) is a rare clinical syndrome due to repeated intracranial hemorrhage. We report a case of SS occurring 19 years after subtotal removal of a non-functioning pituitary adenoma. The patient was a 37-year-old female, exhibiting progressive bilateral sensory neural hearing loss and cerebellar ataxia. T2 weighted magnetic resonance imaging demonstrated a rim of low intensity signal on the cerebellum, brain stem, and sylvian fissure. Immediate diagnosis based on characteristic symptoms and MRI findings is important for the prevention of irreversible progression of SS.